TY - JOUR
T1 - Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats
AU - Zhang, Juan
AU - Tucker, Lorelei Donovan
AU - DongYan,
AU - Lu, Yujiao
AU - Yang, Luodan
AU - Wu, Chongyun
AU - Li, Yong
AU - Zhang, Quanguang
N1 - Funding Information:
This study was supported in part by Research Grant NS086929 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA ; an American Heart Association Grant-in-Aid 15GRNT25240004 ; a Natural Science Foundation of China ( 81403140 ); and a Natural Science Foundation of Shaanxi Province ( 2014JQ4150 ).
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/6
Y1 - 2018/6
N2 - Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury. This study was undertaken to determine the neuroprotective effects and mechanisms of TBHQ post-treatment on neonatal HI brain damage. Using a neonatal HI rat model, we demonstrated that TBHQ markedly abated oxidative stress compared to the HI group, as evidenced by decreased oxidative stress indexes, enhanced Nrf2 nuclear accumulation and DNA binding activity, and up-regulated expression of Nrf2 downstream antioxidative genes. Administration of TBHQ likewise significantly suppressed reactive gliosis and release of inflammatory cytokines, and inhibited apoptosis and neuronal degeneration in the neonatal rat cerebral cortex. In addition, infarct size and neuronal damage were attenuated distinctly. These beneficial effects were accompanied by improved neurological reflex and motor coordination as well as amelioration of spatial learning and memory deficits. Overall, our results provide the first documentation of the beneficial effects of TBHQ in neonatal HI model, in part conferred by activation of Nrf2 mediated antioxidative signaling pathways.
AB - Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury. This study was undertaken to determine the neuroprotective effects and mechanisms of TBHQ post-treatment on neonatal HI brain damage. Using a neonatal HI rat model, we demonstrated that TBHQ markedly abated oxidative stress compared to the HI group, as evidenced by decreased oxidative stress indexes, enhanced Nrf2 nuclear accumulation and DNA binding activity, and up-regulated expression of Nrf2 downstream antioxidative genes. Administration of TBHQ likewise significantly suppressed reactive gliosis and release of inflammatory cytokines, and inhibited apoptosis and neuronal degeneration in the neonatal rat cerebral cortex. In addition, infarct size and neuronal damage were attenuated distinctly. These beneficial effects were accompanied by improved neurological reflex and motor coordination as well as amelioration of spatial learning and memory deficits. Overall, our results provide the first documentation of the beneficial effects of TBHQ in neonatal HI model, in part conferred by activation of Nrf2 mediated antioxidative signaling pathways.
KW - Neonatal hypoxia-ischemia
KW - Neuroprotection
KW - Nrf2
KW - Oxidative stress
KW - Tert-butylhydroquinone
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U2 - 10.1016/j.neuint.2018.03.004
DO - 10.1016/j.neuint.2018.03.004
M3 - Article
C2 - 29530758
AN - SCOPUS:85043454274
SN - 0197-0186
VL - 116
SP - 1
EP - 12
JO - Neurochemistry International
JF - Neurochemistry International
ER -